Abstract: :
Purpose: Primary angle closure (PACG) and open angle (POAG)glaucomas are equally distributed in the south Indian patients.Molecular genetic basis of the disease in this population isless understood and hence this study.Methods: Samples weredrawn from a hospital and population-based screening program.After complete ophthalmic examination DNA from 60 patients [36:POAG,4: Juvenile open angle glaucoma (JAOG) and 20: Ocular hypertension(OHT)] were screened for TIGR/MYOC and optineurin gene mutations.Ninety-five patients (65: POAG, 7: JOAG and 23: OHT) were screenedfor the association of polymorphism in glutathione S transferasegene for glaucoma susceptibility. Fifteen PACG families with2 or more affected members were included for whole genome search(WGS).Results: Six nucleotide variations in the MYOC genewere observed. Two variations in promoter region: C to T at-15 bp and ∐ A between -18 and -17 bp upstream to the transcriptionstart site in fourteen and six patients respectively. Twenty-twopatients with (G to A; N76K) and two patients with (G to T;Q48H) in exon 1; 16 patients with IVS2 795+35 A to G and 5 patientswith + 276 del A in 3' UTR were observed. The novel nucleotidevariation was not seen in thirty-five unrelated healthy controlsbut the other variations were polymorphisms. The frequency ofthe GSTM1 positive individuals among the glaucoma (87%) wassignificantly higher than in controls (56%) with an odds ratioof 5.29 (95% CI 1.85-15.83; p =0.00024). Partial genome searchfor PACG has not resulted in any linkage.Conclusions: TIGR/MYOCgene is responsible for mutations in 2.5% of south Indian OAGpatients. We suggest that GSTM1 polymorphism could be associatedwith the development of OAG. In the WGS, the clinical criteriafor PACG patients are revised for homogeneity.